Human chorionic gonadotropin (hCG) in body fluids of cycling women was investigated for monitoring pregnancy and spontaneous fetal loss. The role of carbohydrate structures in hCG for the gonadotropic action was also the focus of this study. A. A simple procedure for collection, concentration, and a specific urinary hCG radioimmunoassay were applied sucessfully in a pilot study for the detection of early fetal loss in a population of healthy women. In 86 menstrual cycles studies, 19 samples (one sample from each cycle) showed positive hCG level. Among those hCG-positive women, eleven had no detectable level of hCG in the subsequent month indicating early fetal loss. This 58% fetal loss, which is derived from a general population of normal subjects, can be more representative that those of other studies which were carried out in selected groups of women. B. A chemically deglycosylated hCG derivative (HF-hCG) was shown to possess enhanced receptor binding activity but reduced ability to stimulate cyclic AMP and steroid production in gonadal cells. It also antagonized cAMP production in hCG- and FSH-stimulated granulosa cells as well as in hCG-stimulated Leydig cells. Addition of bivalent anti-hCG antibodies, but not their monovalent Fab fragments, to the inactive HF-hCG:LH-receptor complex in differentiated granulosa cells, significantly increased the levels of both cAMP and progesterone production. Since both conformation-specific and sequence-specific hCG-antibodies were equally effective, and antibody bivalency was required to induce the stimulatory effect, cross-linking and microaggregation of the hormone:receptor complex is the most likely cause of target-cell activation by anti-hCG antibodies.